Tools
Stroke-Like Conditions
Introduction
Globally, acute ischemic stroke is the second leading cause of death and the third leading cause of combined death and disability.[1] Ischemic stroke typically presents with the sudden onset of a focal neurological deficit in a vascular distribution, and many noncerebrovascular conditions presenting with acute focal neurological deficits, also called stroke-like conditions or "stroke mimics", can present with similar symptoms, presenting a diagnostic conundrum. These stroke-like conditions account for 20% to 40% of acute stroke cases in the emergency department.[2] Distinguishing an ischemic stroke from potential stroke mimics is extremely time-sensitive, as the 2 available treatments in acute ischemic stroke, pharmacologic thrombolysis and endovascular thrombectomy, are limited by strict timing criteria and contraindications, and the benefit of both these treatments decreases with delays in treatment initiation.[3][4][5]
Stroke mimics are projected to increase substantially in the coming years, resulting in a rise in resource consumption within an already overstretched healthcare system.[6] A potential strategy to decrease the burden of stroke mimics on hospital resources is to increase MRI availability in the acute setting to detect stroke mimics earlier, thus reducing the rate of inappropriate stroke unit admissions and freeing up resources for the treatment of true strokes.[6] Other potential strategies include the development and use of scoring systems to help identify potential stroke mimics, as well as the targeted use of acute MRI in these patients.[7]
This focus on minimizing the time from symptom onset to treatment initiation makes the differentiation between true strokes and stroke-like conditions challenging. Because of the time-sensitive nature of acute stroke diagnosis and the recent emphasis on metrics, eg, "door-to-needle time," a high level of sensitivity for stroke diagnosis is necessary. Consequently, this leads to decreased specificity in the diagnostic evaluation, resulting in an increased number of stroke mimics being evaluated and treated as true ischemic strokes. The treatment for acute strokes is associated with potentially harmful adverse effects, including life-threatening intracranial hemorrhage, highlighting the importance of distinguishing an actual ischemic stroke from a potential stroke mimic. Thus, in this era of "time equals brain," the evaluation and treatment of strokes and stroke-like conditions walk a fine line between timely treatment initiation in acute strokes and overtreatment of stroke mimics.
Etiology
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Etiology
Many conditions can present with acute focal neurological deficits, which may be misdiagnosed as an acute stroke. According to an in-depth review on ischemic stroke mimics, the rate of stroke-like conditions was 24.9% overall. The following conditions or etiologies account for the majority of stroke-like conditions:
- Peripheral vestibular dysfunction (23.2% of cases)
- Toxic-metabolic abnormalities (13.2% of cases)
- Hypoglycemia leads to insufficient energy reserves in brain cells, failing active membrane ion pumps, and, consequently, cytotoxic edema.
- Magnetic resonance imaging (MRI) changes secondary to hypoglycemia may cross several vascular territories, distinguishing them from those caused by cerebrovascular ischemia.[8] Nevertheless, this similarity, even on high-specificity imaging, highlights the importance of immediate blood glucose testing in patients presenting with acute neurological deficits, as this is a rapid and cost-effective method of evaluating for these common stroke-like conditions.
- Seizures (13% of cases) [6]
- Studies identified seizure as the most common cause of stroke-like symptoms, accounting for 17% to 28.5% of cases.[9][10]
- Seizures may present with postictal neurological deficits, known as Todd paralysis.
- Further complicating this situation is the fact that both acute and chronic strokes can cause seizures, making this stroke-like condition very difficult to exclude from an acute stroke presentation.
- Functional disorder or conversion (9.7% of cases)
- One study showed conversion disorder to be a more frequent cause of stroke-like conditions, accounting for 25.7% of cases.[10]
- Migraines (associated with 7.76% of cases)
- Migraine auras may easily be misdiagnosed as an acute stroke, which is especially true in migraine with prolonged aura or migraine equivalent or acephalalgic migraine.
Other etiologies associated with stroke-like conditions include presyncope, sepsis, mononeuropathy, including Bell palsy, space-occupying lesions, acute delirium, dementia, and spinal lesions.[11]
Epidemiology
Estimates of misdiagnosis of strokes range from 5% to 31%.[12][13][14] The most common conditions misdiagnosed as strokes are peripheral vertigo, seizures, and primary headache disorders.[6] Other stroke mimics include intracranial space-occupying lesions, demyelinating disease, movement disorders, sepsis, delirium, metabolic disturbances, hepatic encephalopathy, and functional psychiatric disorders.[7]
History and Physical
Similar to strokes, stroke mimics may present without neurological symptoms, eg, speech difficulties, extremity weakness or numbness, and facial asymmetry. In addition, stroke mimics may exhibit positive neurological symptoms, including aura, hallucinations, or delusions. The presence of these positive symptoms often aids in distinguishing stroke mimics from true strokes.[15]
Overall, patients with stroke-like conditions have significantly lower NIH Stroke Scale scores (4.99 versus 8.06) and are younger (60.9 versus 68.4 years). Additionally, stroke-like conditions have a higher prevalence in females compared to males (60% versus 56%). Patients with stroke-like conditions have been noted to have lower blood pressures (140.25/83.1 versus 153.75/86.45 mm Hg). Loss of consciousness, vomiting, headache, posterior circulation-related symptoms, and normal ability to walk are all more common among patients with stroke-like conditions.[11][16]
Evaluation
Evaluation of Stroke-Like Conditions
The evaluation of stroke-like conditions requires a systematic approach that prioritizes rapid diagnosis while carefully distinguishing true ischemic strokes from stroke mimics.
Laboratory studies
Initial laboratory evaluation plays a critical role in guiding management decisions. Immediate assessment begins with checking blood glucose levels, as hypoglycemia can closely resemble the focal neurological symptoms of a stroke and may exacerbate deficits from prior cerebrovascular events. Prompt correction of hypoglycemia can resolve symptoms and prevent unnecessary interventions. Additional recommended tests include a basic metabolic panel, complete blood count, troponin levels, coagulation studies, and an electrocardiogram. These investigations help rule out metabolic, cardiac, and hematologic conditions that may either mimic stroke or impact treatment decisions, such as eligibility for thrombolysis.
Imaging studies
Noncontrast computed tomography (CT) of the head remains the first-line imaging modality in acute stroke evaluation. Its widespread availability and rapid execution make it essential in the emergency setting. However, due to its limited sensitivity in the first 48 hours of symptom onset, with estimates as low as 12%, a normal CT does not exclude ischemic stroke.[17] Nonetheless, CT successfully identifies 80.2% of ischemic strokes and 57.8% of stroke mimics.[11] CT perfusion imaging enhances diagnostic accuracy by differentiating ischemic penumbra from stroke-like conditions, helping to refine treatment decisions.[18] MRI offers superior sensitivity and specificity for detecting ischemic stroke, especially in its acute stages.[19] Despite this advantage, limited access to MRI in acute care settings often restricts its utility during the critical window for stroke intervention.[19]
Patient characteristics also guide clinicians in differentiating stroke from mimics. Individuals younger than 50, particularly females, and those without classic vascular risk factors, eg, hypertension, atrial fibrillation, diabetes, or hyperlipidemia, are more likely to present with stroke mimics.[6][14] Additional clues include the absence of intracranial atherosclerosis on CT angiography, a lack of focal motor deficits, and a medical history that includes migraines, seizure disorders, or psychiatric illness.[7] Recognition of these features can help prevent the overtreatment of stroke-like conditions while ensuring timely therapy for true strokes.
Treatment / Management
The management approaches for patients presenting with symptoms consistent with an acute stroke that meet strict timing criteria and lack contraindications are thrombolysis or endovascular reperfusion therapy. Studies show that an estimated 4% of patients who receive thrombolytics for a presentation of acute neurological symptoms later receive a diagnosis of a stroke-like condition.[20] Another study showed that 18 of 61 (29%) patients with minor ischemic strokes (NIHSS score of ≤5) and disabling symptoms who received intravenous thrombolytics were finally diagnosed as stroke mimics.[1](A1)
Importantly, studies have repeatedly shown that the administration of thrombolytics in stroke-like conditions carries a more favorable adverse effect profile than the administration of thrombolytics in true ischemic strokes. For example, the risk of symptomatic intracranial hemorrhage following thrombolytic administration in stroke mimics was 0.5% versus 5.2% in true ischemic stroke patients.[20](A1)
Differential Diagnosis
No single historical detail or physical examination finding reliably distinguishes strokes from stroke mimics, which may include metabolic disturbances, migraines, intracranial lesions, seizures, and psychiatric conditions. Stroke mimics can produce neurological deficits confined to a vascular territory, span multiple territories, or follow no vascular pattern at all. While symptom mapping to a specific vascular distribution may assist in identifying true strokes, stroke-like conditions can also align with vascular territories, making this method imperfect.
A gradual onset of symptoms is more suggestive of a stroke-like condition, as actual strokes, except for certain vertebrobasilar events, typically begin abruptly. The presence of positive neurological symptoms, eg, headache, vomiting, or hallucinations, more often indicates a stroke mimic, whereas true strokes usually manifest with negative symptoms like sensory loss or paralysis.[15] A decreased level of consciousness further supports the likelihood of a stroke mimic, particularly in the context of toxic or metabolic encephalopathy.[15]
Prognosis
The prognosis of stroke-like conditions primarily depends on the underlying etiology, as stroke mimics can result from a broad spectrum of diseases. Patients with transient neurological symptoms from conditions (eg, migraines or metabolic derangements) have a better prognosis than those with neurological symptoms from conditions such as multiple sclerosis, sepsis, and decompensated cirrhosis.
Complications
The relatively favorable safety profile of thrombolytic use in stroke mimics has been well-established.[21][22][23] Despite being relatively safe, the administration of thrombolytics in stroke mimics is unnecessary and costly, adding an estimated $5400 to the cost of treatment.[24] The administration of thrombolytic for a stroke-like condition also leads to unnecessary or prolonged hospital stays, additional testing, and unnecessary invasive procedures, further burdening the patient and the healthcare system and using resources that would be more appropriately directed toward true cerebrovascular events. Additionally, while uncommon, complications from thrombolytic administration, such as intracranial hemorrhage and allergic reaction, do exist and contribute to the rate of iatrogenic morbidity and mortality in the healthcare system.
Consultations
The frequency of stroke mimics being misdiagnosed as true strokes is lower in hospitals with higher neurological expertise and those with designated stroke units.[15] Thus, in patients presenting with acute focal neurological deficits, early neurology consultation, when available, is helpful in both diagnostic evaluation and the development of a treatment plan, as well as in determining an appropriate disposition.
Deterrence and Patient Education
Public education campaigns, including the widely recognized FAST campaign (Face-Arm-Speech-Time), promote early recognition of classic stroke symptoms and stress the urgency of seeking immediate medical care.[25] These initiatives aim to reduce delays in treatment by increasing public awareness of the signs of stroke and the critical importance of timely intervention.[25] Rapid response remains essential, regardless of whether the symptoms ultimately stem from an actual ischemic stroke or a stroke mimic, as many stroke mimics present with similar clinical features.
Effective communication with patients diagnosed with stroke mimics plays a vital role in deterrence and long-term education. Clinicians should emphasize that neurological symptoms, even if previously caused by a mimic, warrant immediate medical evaluation if they recur. Many individuals with stroke-like conditions possess underlying risk factors, eg, hypertension, diabetes, or atrial fibrillation, that increase the likelihood of a future ischemic stroke. Ongoing patient education should reinforce the importance of recognizing symptoms, adhering to preventive strategies, and maintaining follow-up care to address modifiable risk factors and ensure early detection of any future cerebrovascular events.
Enhancing Healthcare Team Outcomes
Effective management of stroke and stroke-like conditions demands a coordinated interprofessional approach that leverages the unique skills and responsibilities of physicians, advanced practitioners, nurses, pharmacists, and allied health professionals. Physicians and advanced practitioners, including emergency medicine clinicians and neurologists, must rapidly assess clinical presentation, utilize scoring systems, and interpret imaging to differentiate between true strokes and stroke-like conditions. Nurses with specialized stroke training play a key role in initial triage, neurological assessments, and facilitating urgent diagnostic testing. Pharmacists contribute by ensuring appropriate use of thrombolytics, reviewing contraindications, and supporting safe medication administration, especially when treating patients who may later be identified as stroke mimics. Allied health professionals, including radiology technicians and social workers, support timely imaging and postacute care planning to enhance patient-centered outcomes.
Enhancing access to acute MRI represents a promising strategy to improve diagnostic accuracy and reduce the inappropriate use of stroke units. Increasing MRI availability can lead to earlier identification of stroke mimics, thereby decreasing unnecessary admissions and conserving healthcare resources for patients with true ischemic strokes. Early and consistent communication among team members—including rapid updates between emergency and neurology teams—can streamline care pathways, support early identification of stroke-like conditions, and reduce delays in treatment initiation. This collaborative model not only improves clinical outcomes but also enhances patient safety by avoiding unnecessary interventions and minimizing exposure to potentially harmful therapies. Structured interprofessional communication and care coordination ultimately elevate team performance and ensure efficient, patient-centered management in the high-stakes environment of acute stroke care.
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Level 3 (low-level) evidence